Skip to main content
Top
Published in: Clinical and Translational Oncology 4/2015

01-04-2015 | Research Article

Secretory leukocyte protease inhibitor is a proliferation and survival factor for pancreatic cancer cells

Authors: J. Zuo, C. Zhang, C. Ren, D. Pang, Y. Li, X. Xie, Z. Tang, X. Jiang

Published in: Clinical and Translational Oncology | Issue 4/2015

Login to get access

Abstract

Objectives

A variety of inflammatory cytokines have been demonstrated to participate in tumorigenesis and progression. Secretory leukocyte protease inhibitor (SLPI) has been demonstrated to show a broad-spectrum of anti-inflammatory effects. This study investigates the expression of SLPI in human pancreatic cancer tissues and cells as well as its biological effects in human pancreatic cancer cells.

Methods

Reverse transcription-polymerase chain reaction, immunohistochemistry, and Western blot were used to detect SLPI mRNA and protein levels in human pancreatic cancer tissues, adjacent tissues, and pancreatic cancer Bxpc-3 and Panc-1 cells. Knockout of SLPI expression was established by recombinant viral vector expressing short hairpin RNA (shRNA) targeting SLPI. Cell viability was analyzed by MTT assay. Cell apoptosis was detected by Hochest33258 staining and flow cytometry assay.

Results

Higher SLPI expression was observed in pancreatic tissues, Bxpc-3 cells, and Panc-1 cells compared to the peritumoral tissues (p < 0.01). SLPI expression in Bxpc-3 and Panc-1 cells was effectively silenced by shRNA (p < 0.001). Silencing of SLPI expression significantly reduced cell viability, inhibited cell proliferation, and induced cell apoptosis (p < 0.001).

Conclusions

Abnormal over-expression of SLPI in pancreatic cancer cells may be associated with the development of disease through its roles in promoting cancer cell survival and proliferation as well as anti-apoptosis. SLPI can be used as a target for developing targeted therapy of pancreatic cancer.
Literature
1.
2.
go back to reference Glen P, Jamieson NB, McMillan DC, Carter R, Imrie CW, McKay CJ. Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology. 2006;6:450–3.CrossRefPubMed Glen P, Jamieson NB, McMillan DC, Carter R, Imrie CW, McKay CJ. Evaluation of an inflammation-based prognostic score in patients with inoperable pancreatic cancer. Pancreatology. 2006;6:450–3.CrossRefPubMed
3.
go back to reference Hamada S, Masamune A, Shimosegawa T. Inflammation and pancreatic cancer: disease promoter and new therapeutic target. J Gastroenterol. 2014;49:605–17.CrossRefPubMed Hamada S, Masamune A, Shimosegawa T. Inflammation and pancreatic cancer: disease promoter and new therapeutic target. J Gastroenterol. 2014;49:605–17.CrossRefPubMed
4.
go back to reference Shrikhande SV, Barreto G, Koliopanos A. Pancreatic carcinogenesis: the impact of chronic pancreatitis and its clinical relevance. Indian J Cancer. 2009;46:288–96.CrossRefPubMed Shrikhande SV, Barreto G, Koliopanos A. Pancreatic carcinogenesis: the impact of chronic pancreatitis and its clinical relevance. Indian J Cancer. 2009;46:288–96.CrossRefPubMed
5.
go back to reference Carlson AM, Maurer MJ, Goergen KM, Kalli KR, Erskine CL, Behrens MD, et al. Utility of progranulin and serum leukocyte protease inhibitor as diagnostic and prognostic biomarkers in ovarian cancer. Epidemiol Biomark Prev. 2013;22:1730–5.CrossRef Carlson AM, Maurer MJ, Goergen KM, Kalli KR, Erskine CL, Behrens MD, et al. Utility of progranulin and serum leukocyte protease inhibitor as diagnostic and prognostic biomarkers in ovarian cancer. Epidemiol Biomark Prev. 2013;22:1730–5.CrossRef
6.
go back to reference Hritz I, Kuester D, Vieth M, Herszenyi L, Stolte M, Roessner A, et al. Secretory leukocyte protease inhibitor expression in various types of gastritis: a specific role of helicobacter pylori infection. Eur J Gast Roenterol Hepatol. 2006;18:277–82.CrossRef Hritz I, Kuester D, Vieth M, Herszenyi L, Stolte M, Roessner A, et al. Secretory leukocyte protease inhibitor expression in various types of gastritis: a specific role of helicobacter pylori infection. Eur J Gast Roenterol Hepatol. 2006;18:277–82.CrossRef
7.
go back to reference Antoniades CG, Khamri W, Abeles RD, Taams LS, Triantafyllou E, Possamai LA, et al. Secretory leukocyte protease inhibitor: a pivotal mediator of anti-inflammatory responses in acetaminophen-induced acute liver failure. Hepatology. 2014;59:1564–76.CrossRefPubMed Antoniades CG, Khamri W, Abeles RD, Taams LS, Triantafyllou E, Possamai LA, et al. Secretory leukocyte protease inhibitor: a pivotal mediator of anti-inflammatory responses in acetaminophen-induced acute liver failure. Hepatology. 2014;59:1564–76.CrossRefPubMed
8.
go back to reference Ashcroft GS, Lei K, Jin W, Longenecker G, Kulkarni AB, Greenwell-Wild T, et al. Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing. Nat Med. 2000;6:1147–53.CrossRefPubMed Ashcroft GS, Lei K, Jin W, Longenecker G, Kulkarni AB, Greenwell-Wild T, et al. Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing. Nat Med. 2000;6:1147–53.CrossRefPubMed
9.
go back to reference Choi BD, Jeong SJ, Wang G, Park JJ, Lim DS, Kim BH, et al. Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells. Int J Mol Med. 2011;28:527–34.PubMed Choi BD, Jeong SJ, Wang G, Park JJ, Lim DS, Kim BH, et al. Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells. Int J Mol Med. 2011;28:527–34.PubMed
10.
go back to reference Lin AL, Johnson DA, Stephan KT, Yeh CK. Salivary secretory leukocyte protease inhibitor increases in HIV infection. J Oral Pathol Med. 2004;33:410–6.CrossRefPubMed Lin AL, Johnson DA, Stephan KT, Yeh CK. Salivary secretory leukocyte protease inhibitor increases in HIV infection. J Oral Pathol Med. 2004;33:410–6.CrossRefPubMed
11.
go back to reference Antoniades CG, Khamri W, Abeles RD, Taams LS, Triantafyllou E, Possamai LA, et al. Secretory leukocyte protease inhibitor: a pivotal mediator of anti-inflammatory responses in acetaminophen-induced acute liver failure. Hepatology. 2014;59:1564–76.CrossRefPubMed Antoniades CG, Khamri W, Abeles RD, Taams LS, Triantafyllou E, Possamai LA, et al. Secretory leukocyte protease inhibitor: a pivotal mediator of anti-inflammatory responses in acetaminophen-induced acute liver failure. Hepatology. 2014;59:1564–76.CrossRefPubMed
12.
go back to reference Yang JX, Zhu J, Sun DX, Ding AH. Suppression of macrophage responses to bacterial lipopolysaccharide (LPS) by secretory leukocyte protease inhibitor (SLPI) is independent of its anti-protease function. Biochim Biophys Acta. 2005;1745:310–7.CrossRefPubMed Yang JX, Zhu J, Sun DX, Ding AH. Suppression of macrophage responses to bacterial lipopolysaccharide (LPS) by secretory leukocyte protease inhibitor (SLPI) is independent of its anti-protease function. Biochim Biophys Acta. 2005;1745:310–7.CrossRefPubMed
13.
go back to reference Ma G, Teresa GW, Kejian L, Jin W, Jennifer S, Neil H, et al. Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection. J Exp Med. 2014;200:1337–46.CrossRef Ma G, Teresa GW, Kejian L, Jin W, Jennifer S, Neil H, et al. Secretory leukocyte protease inhibitor binds to annexin II, a cofactor for macrophage HIV-1 infection. J Exp Med. 2014;200:1337–46.CrossRef
14.
go back to reference Reviglio VE, Sambuelli RH, Olmedo A, Falco M, Echenique J, O’Brien TP, et al. Secretory leukocyte protease inhibitor is an inducible antimicrobial peptide expressed in Staphylococcus aureus endophthalmitis. Mediat Inflamm. 2007;2007:93857.CrossRef Reviglio VE, Sambuelli RH, Olmedo A, Falco M, Echenique J, O’Brien TP, et al. Secretory leukocyte protease inhibitor is an inducible antimicrobial peptide expressed in Staphylococcus aureus endophthalmitis. Mediat Inflamm. 2007;2007:93857.CrossRef
15.
go back to reference Zhang X, Lee TH, Davidson C, Lazarus C, Wetsel WC, Ellinwood EH. Reversal of cocaine-induced behavioral sensitization and associated phosphorylation of the NR2B and GluR1 subunits of the NMDA and AMPA receptors. Neuropsychopharmacology. 2007;32:377–87.CrossRefPubMed Zhang X, Lee TH, Davidson C, Lazarus C, Wetsel WC, Ellinwood EH. Reversal of cocaine-induced behavioral sensitization and associated phosphorylation of the NR2B and GluR1 subunits of the NMDA and AMPA receptors. Neuropsychopharmacology. 2007;32:377–87.CrossRefPubMed
16.
go back to reference Shi Y, Hogue J, Dixit D, Koh J, Olson JA Jr. Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia. Proc Natl Acad Sci USA. 2014;111:3092–7.CrossRefPubMedCentralPubMed Shi Y, Hogue J, Dixit D, Koh J, Olson JA Jr. Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia. Proc Natl Acad Sci USA. 2014;111:3092–7.CrossRefPubMedCentralPubMed
17.
go back to reference Ryu B, Jones J, Blades NJ, Parmigiani G, Hollingsworth MA, Hruban RH, et al. Relationships and differentially expressed genes among pancreatic cancers examined by large-scale serial analysis of gene expression. Cancer Res. 2002;62:819–26.PubMed Ryu B, Jones J, Blades NJ, Parmigiani G, Hollingsworth MA, Hruban RH, et al. Relationships and differentially expressed genes among pancreatic cancers examined by large-scale serial analysis of gene expression. Cancer Res. 2002;62:819–26.PubMed
18.
go back to reference Simpkins FA, Devoogdt NM, Rasool N, Tchabo NE, Alejandro EU, Kamrava MM, et al. The alarm anti-protease, secretory leukocyte protease inhibitor, is a proliferation and survival factor for ovarian cancer cells. Carcinogenesis. 2008;29:466–72.CrossRefPubMed Simpkins FA, Devoogdt NM, Rasool N, Tchabo NE, Alejandro EU, Kamrava MM, et al. The alarm anti-protease, secretory leukocyte protease inhibitor, is a proliferation and survival factor for ovarian cancer cells. Carcinogenesis. 2008;29:466–72.CrossRefPubMed
19.
go back to reference Nakamura K, Takamoto N, Hongo A, Kodama J, Abrzua F, Nasu Y, et al. Secretory leukoprotease inhibitor inhibits cell growth through apoptotic pathway on ovarian cancer. Oncol Rep. 2008;19:1085–91.PubMed Nakamura K, Takamoto N, Hongo A, Kodama J, Abrzua F, Nasu Y, et al. Secretory leukoprotease inhibitor inhibits cell growth through apoptotic pathway on ovarian cancer. Oncol Rep. 2008;19:1085–91.PubMed
20.
go back to reference Devoogdt N, Rasool N, Hoskins E, Simpkins F, Tchabo N, Kohn EC. Over-expression of protease inhibitor-dead secretory leukocyte protease inhibitor causes more aggressive ovarian cancer in vitro and in vivo. Cancer Sci. 2009;100:434–40.CrossRefPubMedCentralPubMed Devoogdt N, Rasool N, Hoskins E, Simpkins F, Tchabo N, Kohn EC. Over-expression of protease inhibitor-dead secretory leukocyte protease inhibitor causes more aggressive ovarian cancer in vitro and in vivo. Cancer Sci. 2009;100:434–40.CrossRefPubMedCentralPubMed
21.
go back to reference Choi BD, Jeong SJ, Wang G, Park JJ, Lim DS, Kim BH, et al. Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells. Int J Mol Med. 2011;28:527–34.PubMed Choi BD, Jeong SJ, Wang G, Park JJ, Lim DS, Kim BH, et al. Secretory leukocyte protease inhibitor is associated with MMP-2 and MMP-9 to promote migration and invasion in SNU638 gastric cancer cells. Int J Mol Med. 2011;28:527–34.PubMed
22.
go back to reference Devoogdt N, Hassanzadeh Ghassabeh G, Zhang J, Brys L, De Baetselier P, Revets H. Secretory leukocyte protease inhibitor promotes the tumorigenic and metastatic potential of cancer cells. Proc Natl Acad Sci USA. 2003;100:5778–82.CrossRefPubMedCentralPubMed Devoogdt N, Hassanzadeh Ghassabeh G, Zhang J, Brys L, De Baetselier P, Revets H. Secretory leukocyte protease inhibitor promotes the tumorigenic and metastatic potential of cancer cells. Proc Natl Acad Sci USA. 2003;100:5778–82.CrossRefPubMedCentralPubMed
Metadata
Title
Secretory leukocyte protease inhibitor is a proliferation and survival factor for pancreatic cancer cells
Authors
J. Zuo
C. Zhang
C. Ren
D. Pang
Y. Li
X. Xie
Z. Tang
X. Jiang
Publication date
01-04-2015
Publisher
Springer Milan
Published in
Clinical and Translational Oncology / Issue 4/2015
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-014-1232-4

Other articles of this Issue 4/2015

Clinical and Translational Oncology 4/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine